EP2133356B1 - Verfahren zur herstellung einer phosphorhaltigen ?-ketosäure - Google Patents

Verfahren zur herstellung einer phosphorhaltigen ?-ketosäure Download PDF

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EP2133356B1
EP2133356B1 EP08722570.2A EP08722570A EP2133356B1 EP 2133356 B1 EP2133356 B1 EP 2133356B1 EP 08722570 A EP08722570 A EP 08722570A EP 2133356 B1 EP2133356 B1 EP 2133356B1
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formula
compound
existence
group
compound represented
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EP2133356A4 (de
EP2133356A1 (de
Inventor
Nobuto Minowa
Nozomu Nakanishi
Masaaki Mitomi
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Meiji Seika Pharma Co Ltd
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Meiji Seika Pharma Co Ltd
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/30—Phosphinic acids [R2P(=O)(OH)]; Thiophosphinic acids ; [R2P(=X1)(X2H) (X1, X2 are each independently O, S or Se)]
    • C07F9/301—Acyclic saturated acids which can have further substituents on alkyl

Definitions

  • the present invention relates to a method for producing 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid which is useful as a production intermediate of a herbicide; L-2-amino-4-(hydroxymethylphosphinyl)-butanoic acid (in the below, it is abbreviated as L-AMPB).
  • 3-(alkoxymethylphosphinyl)-propionic acid ester is synthesized such that methyldichlorophosphine is subjected to an addition reaction with acrylic acid, then the produced acid chloride is subjected to a reaction with alcohol (see non-patent documents 3 and 4).
  • the present invention is as follows.
  • a method for producing a compound of formula (6) as a step for producing the compound of formula (4), comprising:
  • a method for producing a compound of formula (6) as a step for producing the compound of formula (4), comprising:
  • a method for producing a compound of formula (6) as a step for producing the compound of the formula (4), comprising a step that the compound of the formula (1) is reacted with isobutylene under the existence of an acid catalyst.
  • a method for producing a compound represented by the following formula (7) said method further including a step that wherein compound of formula (6) is hydrolyzed under the existence of an acid and subjected to decarboxylation.
  • said method comprising:
  • the precursor compound on the process for synthesizing 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid which is a production intermediate of L-AMPB, which is useful as the herbicide, can be produced due to the producing method of the present invention.
  • the producing method of the present invention is superior to the conventional method in a low-cost and efficiency. Therefore, the present invention is extremely industrially useful, especially in the field of pharmaceuticals needed for herbicidal action.
  • C 1-4 alkyl groups shown as R 1 and R 2 mean straight chain or branched alkyl group having 1-4 carbons, in more detail, methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, 2-butyl group, isobutyl group, t-butyl group are listed.
  • the arylmethyl group represented by R 1 and R 2 means methyl group which is substituted by 1 to 3 aryl groups, in more detail, benzyl group, diphenylmethyl group, fluorenyl group, triphenylmethyl group are listed.
  • the substituted arylmethyl group represented by R 1 and R 2 means that one or more hydrogen atom on benzene ring is substituted, preferably 1 to 3 hydrogen atoms are substituted; as a concrete substituted group(s), straight chain or branched C 1-4 alkyl group such as methyl group, ethyl group, n-propyl group, isopropyl group, n-butyl group, 2-butyl group, isobutyl group, t-butyl group; halogen atom such as fluorine atom, chromium atom, bromine atom; and C 1-4 alkoxy group such as methoxy group; are listed.
  • R 1 and R 2 are C 1-4 alkyl group, and more preferably methyl group and ethyl group.
  • the compound of formula (1) can be synthesized by the methods described in JP Kokai Publication 2004-345963A and JP Kokai Publication H05-247068A .
  • ethanol methanol, n-propanol, isopropyl alcohol, n-butanol, benzyl alcohol, and p-methylbenzyl alcohol are listed, and preferably, methanol.
  • methyl iodide ethyl iodide, n-propyl bromide, n-butyl bromide, benzyl bromide, benzyl chloride, and p-methylbenzyl bromide are listed, and more preferably, methyl iodide.
  • oxalic acid dimethylester oxalic acid diethylester, oxalic acid di n-propylester, oxalic acid n-butylester, oxalic acid dibenzylester or oxalic acid di p-methylbenzylester are listed, and oxalic acid dimethylester is preferable.
  • a compound shown below is preferable.
  • the compound of formula (6) has a relation of a tautomer with a compound shown by the following formula (6'), the compound of formula (6) and the compound of formula (6') are existing in equilibrium in a solution. Thereby, in the case where the compound of formula (6) is indicated, it is considered that the compound of formula (6) also includes the structure of the tautomer of the compound of formula (6').
  • halogenated hydrocarbon-based solvent such as methylene chloride and chloroform
  • aromatic hydrocarbon-based solvents such as benzene and toluene alcohol solvent of formula (2)
  • mixed solvents including these two or more than two kinds of solvents described in the above are listed, and preferably, alcohol solvent of formula (2) and mixed solvent of formula (2) and benzene are listed.
  • mineral acids such as hydrochloric acid, sulfuric acid, aromatic sulfonic acids such as p-toluene sulfonic acid, benzene sulfonic acid; and Lewis acids such as trifluoroborate etherate (BF 3 OEt 2 ) are listed.
  • the amount to be used of the acid is 0.01 to 0.3 equivalents based on the amount of the compound of formula (1).
  • the used amount of the compound shown by the formula (2) is 3 to 10 equivalents based on an amount of the compound of formula (1).
  • the reaction temperature is 0 to 130 °C, and preferably, the reaction is performed within a range of 20 and 90 °C.
  • the reaction time is generally 0.1-20 hours, and preferably, the reaction is performed within a range of 0.5 and 10 hours.
  • the generated water is separated by azeotropic distillation using Dean-Stark water separating apparatus, if necessary.
  • reaction solution After finish of the reaction, the reaction solution is concentrated or neutralized with alkali, then generated salt is removed. Thereafter, the compound of formula (4) can be isolated by concentrating the reaction solution. Usually, the reaction solution is used for the next step without the isolation.
  • the producing method of the compound of formula (4) from the compound of formula (1) and the compound of formula (2) under the existence of condensation agent and base is preferably applied to the case where the compound of formula (4) is manufactured from the compound of formula (2) in which R 1 is t-butyl group.
  • Halogenated hydrocarbon-based solvent such as methylene chloride, chloroform; aromatic hydrocarbon-based solvents such as benzene, toluene; ether based solvents such as tetrahydrofuran, dimethoxyethane, dioxane ; ester based solvent such as ethyl acetate; aprotic polar organic solvents such as N,N-dimethyl formamide dimethyl sulfoxide are listed as solvents used in this method, and preferably, methylene chloride is listed.
  • condensation agents carbodiimide based condensation agents such as dicyclohexyl carbodiimide, 1-ethyl-3-(3-(dimethylamino)propyl) carbodiimide hydrochloride are listed, and dimethylaminopyridine is listed as a base.
  • the used amount of the compound shown by formula (2) is 1 to 2 equivalents based on the amount of the compound of formula (1).
  • the reaction temperature is 0 to 130 °C, and preferably, the reaction is performed within a range of 10 and 30 °C.
  • the reaction time is generally 1-20 hours, and preferably, the reaction is performed within a range of 3 and 12 hours.
  • the compound of formula (4) in which R 1 is t-butyl group when manufactured, it can be manufactured by reacting the compound of formula (1) and isobutylene under the existence of an acid catalyst.
  • Halogenated hydrocarbon-based solvents such as methylene chloride, chloroform; aromatic hydrocarbon-based solvents such as benzene, toluene; ether based solvents such as dimethoxyethane and dioxane are listed as solvents used in this reaction, and preferably, methylene chloride is listed.
  • the acid catalyst to be used concentrated sulfuric acid is listed. Isobutylene is used in an excess amount based on the amount of the compound of formula (1).
  • the used amount of the acid is 0.05 to 0.2 equivalents based on the amount of the compound of formula (1).
  • the reaction temperature is 0 to 50 °C, and preferably, the reaction is performed within a range of 20 and 30 °C.
  • the reaction time is usually within a range of 1-48 hours, and preferably, the reaction is performed within a range of 12 and 24 hours.
  • halogenated hydrocarbon-based solvent such as methylene chloride, chloroform
  • aromatic hydrocarbon-based solvents such as benzene, toluene
  • ether based solvents such as tetrahydrofuran, dimethoxyethane, dioxane
  • ketone based solvents such as acetone
  • aprotic polar organic solvents such as N,N-dimethyl formamide and dimethyl sulfoxide
  • alkanol solvents having 1-4 carbons such as methanol
  • sodium hydroxide, potassium hydroxide, sodium carbonate, potassium carbonate, sodium bicarbonate, cesium carbonate, triethylamine and diisopropylethylamine are listed, and preferably, sodium hydrocarbonate is listed.
  • the used amount of the base is 2 to 2.2 equivalents based on the amount of the compound of formula (1).
  • the used amount of the compound shown by the formula (3) is 1 to 1.2 equivalents based on the amount of the compound of formula (1).
  • the reaction temperature is 0 to 100 °C, and preferably, the reaction is performed within a range of 0 and 30 °C.
  • the reaction time is usually within a range of 0.5-24 hours, and preferably, the reaction is performed within a range of 1 and 10 hours.
  • halogenated hydrocarbon-based solvents such as methylene chloride, chloroform
  • aromatic hydrocarbon-based solvents such as benzene, toluene, ether based solvents such as tetrahydrofuran, dimethoxyethane, dioxane
  • aprotic polar organic solvents such as N,N-dimethyl formamide, dimethyl sulfoxide
  • alkanol solvents having 1-4 carbons such as methanol
  • sodium hydride, potassium hydride, sodium methoxide, sodium ethoxide, potassium t-butoxide are listed, and preferably, sodium methoxide is listed.
  • the used amount of the base is 2 to 3 equivalents based on the amount of the compound of formula (4).
  • the amount of use of the compound shown by formula (5) is 1 to 1.6 equivalents based on the amount of the compound of formula (4).
  • the reaction temperature is 0 to 100 °C, and preferably, the reaction is performed within a range of 40 and 60 °C.
  • the reaction time is usually 0.5-12 hours, and preferably, the reaction is performed within a range of 1 and 7 hours.
  • reaction solution After finish of the reaction, the reaction solution is vacuum concentrated after neutralization of the base with diluted hydrochloric acid, and the compound of formula (6) can be isolated by purifying silica gel chromatography. After obtaining crude product by distilling away the reaction solvent; usually, the reaction solution is used for the next step without isolation.
  • hydrochloric acid and sulfuric acid are listed as acids used, and water is listed as a solvent.
  • concentration of acid is in a range of 6-12N in the case where hydrochloric acid is used and in a range of 2-18N in the case where sulfuric acid is used.
  • the reaction temperature is within a range of 20 to 150 °C, and preferably, within a range of 50 to 120 °C.
  • the reaction time is in a range of 2 to 12 hours, and preferably, in a range of 4 to 8 hours.
  • the compound (7) can be isolated and purified using an ion exchange resin (BIO-RAD (registered TRADEMARK) Ag 1x2, eluent:1% trifluoro acetate aqueous solution), for example.
  • BIO-RAD registered TRADEMARK
  • Ag 1x2 eluent:1% trifluoro acetate aqueous solution
  • 4-(hydroxymethylphosphinyl)-2-oxobutanoic acid which is obtainable by the present invention can be converted to L-AMPB according to methods described in JP Kokai Publication H01-027485A , JP Kohyo Publication 2003-528572A , JP Kokai Publication S62-226993A .
  • a solution obtained by dissolving dimethyl oxalate (850mg) in toluene (2ml) was added to a mixed solution of 28% sodium methoxide (2.89g) and toluene (3ml) under ice-cold condition. After stirring for 10 minutes under ice-cold condition, a solution obtained by dissolving methyl 3-(hydroxyl(methyl)phosphinyl) propanoate [-propionate] (996mg) was in toluene (1ml) was added. After stirring for 10 minutes under ice-cold condition, the resultant solution was heated to 50 °C and stirred for 5 hours.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Biochemistry (AREA)
  • General Health & Medical Sciences (AREA)
  • Molecular Biology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Claims (5)

  1. Verfahren zur Darstellung einer Verbindung, welche repräsentiert wird
    durch die folgende Formel (6),
    Figure imgb0024
     [in der Formel repräsentiert R1 eine C1-4-Alkylgruppe, eine Arylmethylgruppe oder eine substituierte Arylmethylgruppe; R2 repräsentiert eine C1-4-Alkylgruppe, eine Arylmethylgruppe oder eine substituierte Arylmethylgruppe];
    wobei eine Verbindung, repräsentiert durch die folgende Formel (4) mit einer Verbindung, repräsentiert durch die folgende Formel (5), zur Reaktion gebracht wird in Gegenwart von 2 bis 3 Äquivalenten einer Base, bezogen auf die Verbindung nach Formel (4).
    Figure imgb0025
     [in der Formel besitzt R1 die gleiche Bedeutung wie zuvor erwähnt]

            (COOR2)2      (5)

    [in der Formel besitzt R2 die gleiche Bedeutung wie zuvor erwähnt], wobei die Base ausgewählt ist aus der Gruppe bestehend aus Natriumhydrid, Kaliumhydrid, Natriummethoxid, Natriumethoxid, Kalium-tert-butoxid.
  2. Verfahren nach Anspruch 1, wobei eine Reaktionstemperatur 40-60 °C beträgt.
  3. Verfahren nach Anspruch 1, wobei ein Schritt zur Darstellung der Verbindung nach der in Anspruch 1 dargelegten Formel (4) umfasst:
    einen Schritt, in welchem eine Verbindung, repräsentiert durch die folgende Formel (1), zur Reaktion gebracht wird mit einer Verbindung, repräsentiert durch die folgende Formel (2), in Gegenwart einer Säure oder in Gegenwart eines Kondensationsmittels und einer Base;
    Figure imgb0026

            R1OH     (2)

    [in der Formel besitzt R1 die gleiche Bedeutung wie dargelegt bei Formel (6) in Anspruch 1]; oder
    einen Schritt, in welchem die Verbindung nach Formel (1) zur Reaktion gebracht wird mit einer durch die folgende Formel (3) repräsentierten Verbindung in Gegenwart einer Base;

            R1X     (3)

    [in der Formel besitzt R1 die gleiche Bedeutung wie dargelegt bei Formel (6) in Anspruch 1, und X repräsentiert ein Halogenatom]; oder
    einen Schritt, in welchem die Verbindung nach Formel (1) mit Isobutylen in Gegenwart eines sauren Katalysators zur Reaktion gebracht wird.
  4. Verfahren nach Anspruch 1, welches ein Verfahren ist zur Darstellung einer durch die folgende Formel (7) repräsentierten Verbindung,
    Figure imgb0027
     wobei das Verfahren ferner einen Schritt umfasst, in welchem die Verbindung nach Formel (6) hydrolysiert wird in Gegenwart einer Säure, um einer Decarboxylierung unterworfen zu werden.
  5. Verfahren zur Darstellung einer Verbindung, repräsentiert durch die folgende Formel (7),
    Figure imgb0028
     wobei das Verfahren umfasst:
    (a) eine Verbindung, repräsentiert durch die folgende Formel (1), wird mit einer Verbindung, repräsentiert durch die folgende Formel (2), zur Reaktion gebracht in Gegenwart einer Säure oder in Gegenwart eines Kondensationsmittels und einer Base
    Figure imgb0029
             R1OH     (2)

    [in der Formel repräsentiert R1 eine C1-4-Alkylgruppe, eine Arylmeethylgruppe oder eine substituierte Arylmethylgruppe]; oder
    die Verbindung nach Formel (1) wird mit einer Verbindung, repräsentiert durch die folgende Formel (3), in Gegenwart einer Base zur Reaktion gebracht

            R1X     (3)

    [in der Formel besitzt R1 die gleiche Bedeutung wie zuvor erwähnt, und X repräsentiert ein Halogenatom]; oder
    die Verbindung nach Formel (1) wird mit Isobutylen in Gegenwart eines sauren Katalysators zur Reaktion gebracht;
    um eine Verbindung, repräsentiert durch die folgende Formel (4), darzustellen;
    Figure imgb0030
     [in der Formel besitzt R1 die gleiche Bedeutung wie zuvor erwähnt],
    danach wird
    (b) die Verbindung nach Formel (4) zur Reaktion gebracht mit einer Verbindung, repräsentiert durch die folgende Formel (5), in Gegenwart von 2-3 Äquivalenten einer Base, bezogen auf die Verbindung nach Formel (4), wobei die Base ausgewählt ist aus der Gruppe bestehend aus Natriumhydrid, Kaliumhydrid, Natriummethoxid, Natriumethoxid, Kalium-tert-butoxid;

            (COOR2)2      (5)

    [in der Formel repräsentiert R2 eine C1-4-Alkylgruppe, eine Arylmethylgruppe oder eine substituierte Arylmethylgruppe] um eine Verbindung darzustellen, repräsentiert durch die folgende Formel (6);
    Figure imgb0031
     [in der Formel besitzen R1 und R2 die gleiche Bedeutung wie zuvor erwähnt]; und ferner wird
    (c) die Verbindung nach Formel (6) hydrolysiert in Gegenwart einer Säure, um einer Decarboxylierung unterworfen zu werden.
EP08722570.2A 2007-03-23 2008-03-21 Verfahren zur herstellung einer phosphorhaltigen ?-ketosäure Not-in-force EP2133356B1 (de)

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JP2007076541 2007-03-23
PCT/JP2008/055206 WO2008117733A1 (ja) 2007-03-23 2008-03-21 リン含有α－ケト酸の製造法

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EP2133356A4 EP2133356A4 (de) 2011-08-17
EP2133356B1 true EP2133356B1 (de) 2014-09-24

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US (1) US8017797B2 (de)
EP (1) EP2133356B1 (de)
JP (1) JP5368971B2 (de)
CN (2) CN101641363A (de)
ES (1) ES2525798T3 (de)
IL (1) IL200945A (de)
WO (1) WO2008117733A1 (de)

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AU2011266126B2 (en) 2010-06-15 2014-12-11 Meiji Seika Pharma Co., Ltd. Method for producing N-substituted-2-amino-4-(hydroxymethylphosphinyl)-2-butenoic acid
CN103665032B (zh) * 2013-12-09 2016-02-17 江苏七洲绿色化工股份有限公司 一种草铵膦的制备方法
CN105175443B (zh) * 2015-08-17 2017-04-19 湖南海利化工股份有限公司 一种含磷α酮酸酯的制备方法
CN106279270A (zh) * 2016-08-08 2017-01-04 安徽国星生物化学有限公司 一锅法制备4‑(甲基羟基磷酰基)‑2‑羰基丁酸的方法
CN110343676B (zh) 2018-04-03 2020-06-23 上海弈柯莱生物医药科技有限公司 一种l-谷氨酸脱氢酶突变体及其应用
CN109369710B (zh) * 2018-10-26 2020-10-09 洪湖市一泰科技有限公司 一种4-(甲基羟基磷酰基)-2-羰基丁酸的高效纯化工艺
CN111979208B (zh) 2019-05-23 2023-01-10 弈柯莱生物科技(上海)股份有限公司 一种l-谷氨酸脱氢酶突变体及其应用
CN111690002A (zh) * 2020-04-29 2020-09-22 洪湖市一泰科技有限公司 锂盐化合物及其制备方法和包含其的锂离子电池电解液
CN117700451A (zh) * 2022-09-08 2024-03-15 浙江新安化工集团股份有限公司 一种4-(羟基甲基膦酰基)-2-羰基丁酸的制备方法
CN117700450A (zh) * 2022-09-08 2024-03-15 浙江新安化工集团股份有限公司 一种4-(羟基甲基膦酰基)-2-羰基丁酸的制备方法

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IL200945A0 (en) 2010-05-17
JPWO2008117733A1 (ja) 2010-07-15
IL200945A (en) 2012-05-31
WO2008117733A1 (ja) 2008-10-02
CN101641363A (zh) 2010-02-03
ES2525798T3 (es) 2014-12-30
CN104761583A (zh) 2015-07-08
US8017797B2 (en) 2011-09-13
JP5368971B2 (ja) 2013-12-18
EP2133356A4 (de) 2011-08-17
US20100063313A1 (en) 2010-03-11
EP2133356A1 (de) 2009-12-16

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